The American Society of Hematology (ASH) annual meeting is the premier scientific forum on blood cancers. More than 5,000 potentially game-changing research abstracts were presented at this year’s meeting. Every year, I come away with a strengthened sense of hope about new treatments on the horizon and renewed pride in The Leukemia & Lymphoma Society’s (LLS) role in supporting so many of them.
The biggest story again this year is the stunning advances in our ability to harness the body’s immune system to fight blood cancers. Our growing knowledge is paving the way for newer, even more precise immunotherapy approaches, including an increasing number of CAR-T therapies, bispecific antibodies, and other immune-based approaches that can treat even more types of blood cancer and earlier in the treatment process.
Beginning in the 1990’s, LLS was one of the earliest and leading supporters of the foundational science that is the basis for all CAR-T immunotherapies that have followed. We continue to invest heavily in immunotherapy, dedicating more than $100 million to investigate game changing, next generation treatments.
These and other exciting advances were featured at this year’s conference.
New treatment options for aggressive forms of lymphoma with high unmet need
About 60% of patients with the most common form of lymphoma, diffuse large B-cell lymphoma (DLBCL) can expect a cure with conventional therapy. This year’s ASH meeting provided a great deal of hope for the 4 in 10 patients who don’t fall into this category. Two noteworthy phase 3 CAR-T immunotherapy trials reported results in DLBCL patients whose disease relapsed or worsened after one earlier treatment.
Frederick Locke, M.D (Moffitt Cancer Center, FL)., a LLS Scholar in Clinical Research grantee, reported that the CAR-T therapy axi-cel (Yescarta®) improved event-free survival in these patients by four times—8.3 months compared with 2.3 months with the standard of care chemotherapy. In a second trial, CAR-T therapy liso-cel (Breyanzi®) improved event-free survival to 10.1 months compared with 2.3 months with standard-of-care.
Another trial evaluated axi-cel used even earlier in patient care—as front-line (first treatment) for patients diagnosed with high-risk DLBCL. The ZUMA-12 trial, (presented by two LLS-funded investigators working on other novel CAR T projects), reported a 78% complete response rate — that is, disappearance of all signs of cancer in the body, with 75% of patients showing no signs of cancer progression after a full year. Given how well CAR-T therapies work in patients at later stages of the disease, this is convincing data for the use of CAR-T earlier in the disease.
With eight current approvals, CAR-T immunotherapy is a game changer for many patients, but there is still more work to be done. It can take about a month to prepare CAR-T cells for an individual patient before treatment can begin. In contrast, treatment with bispecific antibodies, which also harnesses the immune system to fight cancer, can start immediately.
Researchers presented results of two trials testing bispecific antibodies in patients whose follicular lymphoma worsened or returned after previous treatment. The trials reported complete response rates in 54% to 60% of patients receiving the treatment. These results are similar to currently approved CAR-T therapies. The ability to control the disease for a long duration is encouraging.
Three trials were presented that test different types of drugs in mantle cell lymphoma, a rare and aggressive form of lymphoma that tends to have a poor prognosis. All three drugs: a bispecific antibody, a targeted treatment that inhibits a protein called Bruton Tyrosine Kinase, and a third that combines an antibody with an anti-tumor agent, reported positive findings. With no standard treatment currently available for these patients, these results are very welcome news. These new alternatives add to CAR T-therapy, which is already approved for MCL patient who relapse. CAR-T therapy in MCL patients demonstrated marked efficacy even in patients who had high grade disease that were ineligible for the pivotal clinical study that leads to the FDA approval. LLS will be keeping an eye on the progress of all three new medications.
Treatment advances for multiple myeloma and leukemia
We reached a big milestone this past March with approval of the first CAR-T therapy for multiple myeloma, ide-cel (Abecma™). LLS is supporting research conducted by Madhav V. Dhodapkar, MBBS at Emory University in Atlanta to enhance the activity of this breakthrough drug.
Reports at ASH included another BCMA-targeting CAR-T therapy called cilta-cel, which looks promising and may offer advantages over ide-cel. However, results of the two therapies haven’t been tested head-to-head. There were also reports about two bispecific antibodies, teclistamab and elranatamab for multiple myeloma treatment and an “off the shelf” CAR-T therapy that could shorten the time it takes to start treatment, and that may help reduce treatment cost.
Nearly one quarter of LLS research dollars are dedicated to hard-to-treat acute myeloid leukemia. LLS funding helped identify a rare and lethal subtype of AML that includes rearrangement of certain genes. This led to development of several targeted treatments that attack this specific AML subtype. Data presented on SNDX-5613 at ASH demonstrated a complete response rate of 44% among patients with this particularly hard-to-treat cancer.
Our research has also helped uncover that, like viruses, AML can change over time and is marked by specific genetic mutations that can be key to treatment failures—or success. The phase 3, AGILE trial presented at ASH reported that a combination treatment with a drug that inhibits a specific mutated protein called IDH1 along with a chemotherapy agent tripled average survival times compared to the chemotherapy drug alone, from 7.9 months to two years.
Deeper understanding of cancer genetics can help identify future risks
Genetics is not just helping us develop targeted treatments, it is helping researchers identify—and hopefully plan for—future risk of blood cancer. For example, LLS funded researcher Dr. George Vassiliou (University of Cambridge, UK) discovered that over-production of a certain cell in the bone marrow could help identify individuals at high risk of AML years before the illness actually begins.
Research building on this finding was presented at ASH, providing further insights into which of these cells put you at higher risk, and which ones are lower risk. This can help individuals and their healthcare team decide on the best way to monitor them and decide when and if treatment is warranted.
Another LLS scholar investigator, Dr. Arash Alizadeh (Stanford University, California), presented new data about genetic testing that can determine whether patients with certain forms of lymphoma will relapse. This includes blood tests that are 80% to 90% accurate in predicting DLBCL relapse up to six months before it happens, and another blood test that can diagnose lymphoma in the central nervous, helping patients avoid invasive and difficult brain biopsy. And if blood tests weren’t easy enough, Alizadeh and colleagues are also working on a test that can find genetic mutations in saliva that can tell if someone is at risk of developing follicular lymphoma.
I think you can see why I come away from ASH every year with a strengthened sense of hope and pride. And remember, these are just some of the many promising treatments and tests on the horizon.
I also discussed these updates from ASH on Treating Blood Cancers: The LLS Podcast Series for Professionals. You can listen to the episode here: https://treatingbloodcancers.org/e50/.